Association of Gout Polygenic Risk Score With Age at Disease Onset and Tophaceous Disease in European and Polynesian Men With Gout.

Autor: Sumpter NA; Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, and Department of Biochemistry, University of Otago, Dunedin, New Zealand., Takei R; Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham., Cadzow M; Department of Biochemistry, University of Otago, Dunedin, New Zealand., Topless RKG; Department of Biochemistry, University of Otago, Dunedin, New Zealand., Phipps-Green AJ; Department of Biochemistry, University of Otago, Dunedin, New Zealand., Murphy R; Department of Medicine, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand., de Zoysa J; Department of Medicine, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand., Watson H; Ngāti Porou Hauora Trust, Te Puia Springs, New Zealand., Qasim M; Ngāti Porou Hauora Trust, Te Puia Springs, New Zealand., Lupi AS; Department of Epidemiology and Biostatistics, Michigan State University, and The Institute for Quantitative Health Science & Engineering, Michigan State University, East Lansing, Michigan., Abhishek A; Academic Rheumatology, School of Medicine, University of Nottingham, Nottingham City Hospital, Nottingham, UK, and GlobalGoutGenetics Consortium., Andrés M; GlobalGoutGenetics Consortium, and Department of Rheumatology, Alicante General University Hospital-ISABIAL, Miguel Hernandez University, Alicante, Spain., Crișan TO; GlobalGoutGenetics Consortium, and Department of Medical Genetics, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania., Doherty M; Academic Rheumatology, School of Medicine, University of Nottingham, Nottingham City Hospital, Nottingham, UK, and GlobalGoutGenetics Consortium., Jacobsson L; GlobalGoutGenetics Consortium, and Department of Rheumatology & Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Sweden., Janssen M; GlobalGoutGenetics Consortium, and Complex Gout Expert Centre, Department of Rheumatology, Viecuri Medical Centre, Venlo, The Netherlands., Jansen TL; GlobalGoutGenetics Consortium, and Complex Gout Expert Centre, Department of Rheumatology, Viecuri Medical Centre, Venlo, The Netherlands., Joosten LAB; GlobalGoutGenetics Consortium, and Department of Medical Genetics, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania, and Department of Internal Medicine, Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, The Netherlands., Kapetanovic M; GlobalGoutGenetics Consortium, and Lund University and Skåne University Hospital, Lund, Sweden., Lioté F; Department of Medicine, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand., Matsuo H; GlobalGoutGenetics Consortium, and Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Saitama, Japan., McCarthy GM; GlobalGoutGenetics Consortium, and Mater Misericordiae University Hospital and University College, Dublin, Ireland., Perez-Ruiz F; GlobalGoutGenetics Consortium, and Rheumatology Division, Osakidetza, OSI EE-Cruces, Cruces University Hospital, Barakaldo, Biocruces-Bizkaia Health Research Institute, Barakaldo, and the Medicine Department of the Medicine School of the University of the Basque Country, Leioa, Spain., Riches P; GlobalGoutGenetics Consortium, and IGC, University of Edinburgh, Scotland., Richette P; GlobalGoutGenetics Consortium, and Hôpital Lariboisière, Assistance Publique-Hopitaux de Paris, and INSERM UMR-1132 and Université Paris Cité, Paris, France., Roddy E; GlobalGoutGenetics Consortium, and School of Medicine, Keele University, Keele, Staffordshire, UK., Stiburkova B; GlobalGoutGenetics Consortium, and Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic, and Institute of Rheumatology, Prague, Czech Republic., So A; GlobalGoutGenetics Consortium, and Service of Rheumatology, Department of Musculoskeletal Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland., Tausche AK; GlobalGoutGenetics Consortium, and Division of Rheumatology, University Clinic Carl Gustav Carus at the TU Dresden, Dresden, Germany., Torres RJ; GlobalGoutGenetics Consortium, and Department of Biochemistry, La Paz University Hospital Health Research Institute (FIBHULP), IdiPaz, and Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain., Uhlig T; GlobalGoutGenetics Consortium, and Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway., Major TJ; Department of Biochemistry, University of Otago, Dunedin, New Zealand., Stamp LK; GlobalGoutGenetics Consortium, and Department of Medicine, University of Otago, Christchurch, New Zealand., Dalbeth N; Department of Medicine, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand, and GlobalGoutGenetics Consortium., Choi HK; Clinical Epidemiology Unit, Massachusetts General Hospital, Boston., Vazquez AI; Department of Epidemiology and Biostatistics, Michigan State University, and The Institute for Quantitative Health Science & Engineering, Michigan State University, East Lansing, Michigan., Leask MP; Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham., Reynolds RJ; Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham., Merriman TR; Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Department of Biochemistry, University of Otago, Dunedin, New Zealand, and GlobalGoutGenetics Consortium.
Jazyk: angličtina
Zdroj: Arthritis & rheumatology (Hoboken, N.J.) [Arthritis Rheumatol] 2023 May; Vol. 75 (5), pp. 816-825. Date of Electronic Publication: 2023 Mar 25.
DOI: 10.1002/art.42393
Abstrakt: Objective: To determine whether a gout polygenic risk score (PRS) is associated with age at gout onset and tophaceous disease in European, East Polynesian, and West Polynesian men and women with gout.
Methods: A 19-variant gout PRS was produced in 7 European gout cohorts (N = 4,016), 2 East Polynesian gout cohorts (N = 682), and 1 West Polynesian gout cohort (N = 490). Sex-stratified regression models were used to estimate the relationship between the PRS and age at gout onset and tophaceous disease.
Results: The PRS was associated with earlier age at gout onset in men (β = -3.61 in years per unit PRS [95% confidence interval (95% CI) -4.32, -2.90] in European men; β = -6.35 [95% CI -8.91, -3.80] in East Polynesian men; β = -3.51 [95% CI -5.46, -1.57] in West Polynesian men) but not in women (β = 0.07 [95% CI -2.32, 2.45] in European women; β = 0.20 [95% CI -7.21, 7.62] in East Polynesian women; β -3.33 [95% CI -9.28, 2.62] in West Polynesian women). The PRS showed a positive association with tophaceous disease in men (odds ratio [OR] for the association 1.15 [95% CI 1.00, 1.31] in European men; OR 2.60 [95% CI 1.66, 4.06] in East Polynesian men; OR 1.53 [95% CI 1.07, 2.19] in West Polynesian men) but not in women (OR for the association 0.68 [95% CI 0.42, 1.10] in European women; OR 1.45 [95% CI 0.39, 5.36] in East Polynesian women). The PRS association with age at gout onset was robust to the removal of ABCG2 variants from the PRS in European and East Polynesian men (β = -2.42 [95% CI -3.37, -1.46] and β = -6.80 [95% CI -10.06, -3.55], respectively) but not in West Polynesian men (β = -1.79 [95% CI -4.74, 1.16]).
Conclusion: Genetic risk variants for gout also harbor risk for earlier age at gout onset and tophaceous disease in European and Polynesian men. Our findings suggest that earlier gout onset involves the accumulation of gout risk alleles in men but perhaps not in women, and that this genetic risk is shared across multiple ancestral groups.
(© 2022 American College of Rheumatology.)
Databáze: MEDLINE
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